New Molecular-Mechanics Model for Simulations of Hydrogen Fluoride in Chemistry and Biology

Abstract

Hydrogen fluoride (HF) is the most polar diatomic molecule and one of the simplest molecules capable of hydrogen-bonding. HF deviates from ideality both in the gas phase and in solution and is thus of great interest from a fundamental standpoint. Pure and aqueous HF solutions are broadly used in chemical and industrial processes, despite their high toxicity. HF is a stable species also in some biological conditions, because it does not readily dissociate in water unlike other hydrogen halides; yet, little is known about how HF interacts with biomolecules. Here, we set out to develop a molecular-mechanics model to enable computer simulations of HF in chemical and biological applications. This model is based on a comprehensive high-level ab initio quantum chemical investigation of the structure and energetics of the HF monomer and dimer; (HF) n clusters, for n = 3–7; various clusters of HF and H2O; and complexes of HF with analogs of all 20 amino acids and of several commonly occurring lipids, both neutral and ionized. This systematic analysis explains the unique properties of this molecule: for example, that interacting HF molecules favor nonlinear geometries despite being diatomic and that HF is a strong H-bond donor but a poor acceptor. The ab initio data also enables us to calibrate a three-site molecular-mechanics model, with which we investigate the structure and thermodynamic properties of gaseous, liquid, and supercritical HF in a wide range of temperatures and pressures; the solvation structure of HF in water and of H2O in liquid HF; and the free diffusion of HF across a lipid bilayer, a key process underlying the high cytotoxicity of HF. Despite its inherent simplifications, the model presented significantly improves upon previous efforts to capture the properties of pure and aqueous HF fluids by molecular-mechanics methods and to our knowledge constitutes the first parameter set calibrated for biomolecular simulations.

Twisted Intramolecular Charge Transfer (TICT) Controlled by Dimerization: An Overlooked Piece of the TICT Puzzle

“…Intermolecular interactions and its impact on the absorption spectra of L1 were investigated by using the (L1) 2 dimer as a model. The S 0 geometry of the (L1) 2 dimer was optimized in the gas phase starting from various initial binding conformations, and the interaction energies of all stable structures (no imaginary frequencies) are calculated − without ( E ) and with ( E CP ) correction for basis set superposition error (BSSE) by using the counterpoise procedure of Boys and Bernardi …”

Unusually Large Hydrogen-Bond Cooperativity in Hydrogen Fluoride Clusters, (HF)n,n= 3 to 8, Revealed by the Molecular Tailoring Approach

“…However, in the gas phase, the cyclic structures are more stable than the linear (HF) n ( n ≥ 3) ones due to the formation of one extra HB as compared to its linear counterparts. In the present work, the mPW1B95/6-31+G­(d,p) level optimized geometries of cyclic hydrogen fluoride clusters, C-(HF) n , n = 3 to 8, were taken from ref and those of linear L-(HF) n , n = 2 to 8, were obtained from ref . We reoptimized these geometries of the L-(HF) n and C-(HF) n clusters at the MP2/aug-cc-pVDZ (hereafter called as MP2/aVDZ) level.…”

“…17−19 However, there is very little information available on how HF interacts with proteins and other cellular components. 20 Therefore, it is indispensable to investigate the molecular geometry and the strength of HBs in (HF) n -clusters to shed light on these solvation processes. Various attempts have been directed toward understanding the HB interactions in HF clusters.…”

“…HF is used as a starting material for the preparation of various fluorine-containing refrigerants and also in the synthesis of inorganic fluorides. , It is also used in uranium enrichment, aluminum manufacturing, and as a catalyst in the production of high-octane gasoline . Owing to its low acidity, HF is an excellent solvent: proteins and carbohydrates can be dissolved and recovered from it. − However, there is very little information available on how HF interacts with proteins and other cellular components . Therefore, it is indispensable to investigate the molecular geometry and the strength of HBs in (HF) n -clusters to shed light on these solvation processes.…”

Mechanisms Underlying Proton Release in CLC-type F–/H+ Antiporters

“…Fluoride can permeate cell membranes as HF, in contrast to other anions such as Cl – and NO 3 – . HF is a weak acid (p K a ∼ 3.2) that does not dissociate completely in water.…”